INTOarthritis: Identifying New Treatment targets for Osteoarthritis using multiomic data and next generation personalised human in vitro models



Osteoarthritis (OA) is a heterogeneous disease, resulting in different osteoarthritis subtypes with different underlying mechanisms. This means that each individual patient can have a different (combination of) cause and mechanism of disease. This disease heterogeneity has hampered the development of effective therapies for osteoarthritis. We here propose to use the combination of large-scale multi-omics data and individualised in vitro cellular models to accelerate the translation from discovery of novel therapeutic targets into personalised treatment of osteoarthritis (precision medicine). Using large-scale existing and novel genomic data, we will identify possible novel etiological mechanisms underlying osteoarthritis. These mechanisms will be validated by next-generation cellular in vitro models of disease that will take into account genetic differences and will be tailored to the etiological mechanisms under study such as inflammation and mechanical loading. This will lead to candidates for new treatments for defined groups of patients. These will be tested in the developed in vitro models. Our approach is therefore optimised to develop precision medicine to stop or reverse osteoarthritis and thus contribute to the ambition of the DAS to turn osteoarthritis into a non-chronic, reversible disease.
Main goals
This project will focus on 4 research areas:
1)    A multi-omics discovery pipeline for Osteoarthritis target identification.
2)    Development of personalised models: a population-in-a-dish.
3)    Next generation osteoarthritis models: towards causal mechanisms.
4)    Osteoarthritis treatment testing (in silico and in vitro)